The multi-functionality of CD40L and its receptor CD40 in atherosclerosis

Dirk Lievens; Wouter J. Eijgelaar; Erik A. L. Biessen; Mat J. A. P. Daemen; Esther Lutgens

doi:10.1160/TH09-01-0029

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2009; 102(02): 206-214
DOI: 10.1160/TH09-01-0029

Theme Issue Article

Schattauer GmbH

The multi-functionality of CD40L and its receptor CD40 in atherosclerosis

Autor*innen

Dirk Lievens

¹Experimental Vascular Pathology Division (EVP), Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) University of Maastricht, The Netherlands
Wouter J. Eijgelaar

¹Experimental Vascular Pathology Division (EVP), Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) University of Maastricht, The Netherlands
Erik A. L. Biessen

¹Experimental Vascular Pathology Division (EVP), Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) University of Maastricht, The Netherlands
Mat J. A. P. Daemen

¹Experimental Vascular Pathology Division (EVP), Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) University of Maastricht, The Netherlands
Esther Lutgens

¹Experimental Vascular Pathology Division (EVP), Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM) University of Maastricht, The Netherlands

²Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany

Abstract

Summary

Disrupting the CD40-CD40L co-stimulatory pathway reduces atherosclerosis and induces a stable atherosclerotic plaque phenotype that is low in inflammation and high in fibrosis. Therefore, inhibition of the CD40-CD40L pathway is an attractive therapeutic target to reduce clinical complications of atherosclerosis. The CD40-CD40L dyad is known to interact with other costimulatory molecules, to activate antigen-presenting cells (APC) and to contribute to T-cell priming and B-cell isotype switching. Besides their presence on T-cells and APCs, CD40 and CD40L are also present on macrophages, endothelial cells and vascular smooth muscle cells in the plaque, where they can exert pro-atherogenic functions. Moreover, recent progress indicates the involvement of neutrophil CD40, platelet CD40L and dendritic cell CD40 in atherogenesis. Since systemic CD40-CD40L modulation compromises host defense, more targeted interventions are needed to develop superior treatment strategies for atherosclerosis. We believe that by unravelling the cell-cell CD40-CD40L interactions, inhibition of cell-type specific (signalling components of) CD40(L) that do not compromise the patient’s immune system, will become possible. In this review, we highlight the cell-type specific multi-functionality of CD40-CD40L signalling in atherosclerosis.

Keywords

Atherosclerosis - immunity - inflammation - co-stimulation - TNF receptor-associated factor

Volltext

Referenzen

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